Abstract: e20550 Background: Patient selection, dosing regimens and resistance mechanisms for immune checkpoint inhibitor combination therapy remain unmet medical needs in lung cancer. Combining blockade of PD-1 and CTLA-4 can be more effective than monotherapy but is accompanied by an increase in toxicity. Thus, to circumvent unnecessary toxicity it is of great interest to identify patients who will benefit from PD-1/PD-L1 blockade alone and to add ipilimumab only in case of primary or secondary progression. We present interim data from the non-small-cell lung cancer (NSCLC) cohort of the ongoing BIOLUMA trial which evaluates efficacy and safety of nivolumab and ipilimumab in lung cancer with a broad translational program to identify potential biomarkers predictive of response and/or resistance including whole exome sequencing (WES) of serial biopsies, functional analysis of peripheral T-cells and gut microbiome analyses. Methods: BIOLUMA is a multicentre non-randomised phase II trial in 2 nd line patients with non-squamous NSCLC. Patients are treated with nivolumab 240 mg until disease progression and subsequently with a combination therapy of nivolumab 3 mg/kg q2w and ipilimumab 1mg/kg q6w. Primary endpoint is overall response rate (ORR) after addition of ipilimumab to nivolumab treatment. Analysis of sequential tumor biopsies, blood and gut microbiome is performed at different timepoints. Results: To date, 26 patients have been enrolled and 9 patients were transferred to the combination therapy after progression on nivolumab monotherapy. Drop out rate between the treatment arms is high, mainly due to rapid disease progression and adverse events which don’t allow addition of ipilimumab. ORR is available for 8 of these patients: 6 patients (75%) had PD as best response, and 1 (12.5%) each had a stable disease and partial response, respectively. The patient who achieved a PR had experienced primary tumor progression on nivolumab monotherapy before. Toxicity rate was similar to what has been reported from other trials. Conclusions: In NSCLC, addition of ipilimumab to nivolumab in nivolumab refractory patients seems to be safe, but the response rate is low and the drop out between the treatment parts high. Given these data, early termination of this cohort is currently discussed. Clinical trial information: NCT03083691.

Abstract: 8563 Background: Patient selection, dosing regimens and resistance mechanisms for immune checkpoint inhibitor combination therapy remain unmet medical needs in lung cancer. We present interim data from the small-cell lung cancer (SCLC) cohort of the ongoing BIOLUMA trial which evaluates efficacy and safety of nivolumab and ipilimumab in lung cancer with a broad translational program to identify potential biomarkers predictive of response and/or resistance including whole exome sequencing (WES) of serial biopsies, functional analysis of peripheral T-cells and gut microbiome analyses. Methods: BIOLUMA is an investigator initiated, multicentre non-randomised phase II trial in 2 nd line patients with SCLC. The initial all-comer SCLC cohort was recently amended for inclusion of patients with high tumor mutation burden (TMB) only. Patients are pre-screened for TMB by WES at the time of first diagnosis. After progression on platinum-based therapy, 4 cycles of nivolumab 1 mg/kg q3w in combination with ipilimumab 3 mg/kg q3w and subsequent nivolumab 240 mg flat dose as monotherapy are given. Primary endpoint is overall response rate (ORR) of the upfront combination therapy. Analysis of sequential tumor biopsies, blood and gut microbiome is performed at different timepoints. Results: The SCLC cohort was amended to include TMB high patients only, after two treatment-related deaths had occurred and emerging data indicated treatment benefit depends on high TMB status for the combination therapy. Both patients with treatment-related death had a CT-scan documented partial response (not confirmed according to RECIST due to death). One each died of pneumonitis and encephalitis. From the all-comer cohort, efficacy data are available for 18 patients. ORR was 38.8% with 7 partial and no complete responses. Stable disease occurred in 16.7% (n = 3) resulting in a DCR of 55.5%. TMB pre-screening for the amended cohort is currently ongoing. Conclusions: In the SCLC cohort, upfront combination therapy of nivolumab and ipilimumab shows remarkable ORR but is accompanied by high toxicity rates. In order to ensure a reasonable balance of risks and treatment benefit, only TMB high patients are included after an amendment of the cohort to improve the risk/benefit ratio. Clinical trial information: NCT03083691.

Abstract: Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome emerging from a deregulated immune response due to various triggers. In adults, systematic data are sparse, which is why recommendations on diagnosis and management have been adopted from pediatric guidelines. A nationwide clinical registry with associated consulting service as collaborative initiative of HLH-specialized pediatricians and hematologists was initiated to better characterize HLH in adults. Methods Patients with proven or suspected HLH were registered by 44 institutions. Both HLH-2004 diagnostic criteria and the HScore ( www.saintantoine.aphp.fr/score/ ) were used to confirm HLH diagnosis. Data referring to underlying disease, treatment, outcome, clinical presentation and laboratory findings were recorded. Results The study included 137 patients and provides the first systematic data on adult HLH in Germany. Median age was 50 years with a wide range (17–87 years), 87 patients (63.5%) were male. Most common triggering diseases were infections in 61 patients (44.5%) and malignancies in 48 patients (35%). Virtually all patients had elevated ferritin concentrations, and 74% had peak concentrations greater than 10,000 µg/l. At time of analysis, 67 of 131 patients (51%) had died. Patients with malignancy-associated HLH had the shortest median survival (160 days), however no statistically significant difference between subgroups was observed ( p  = 0.077). Platelets under 20*10 9 /l and low albumin concentrations ( 〈  20 g/l) were associated with poor overall and 30-day survival. Conclusion Close multidisciplinary case consultation and cooperation is mandatory when treating adult HLH patients. Early contact with reference centers is recommended, especially in relapsing or refractory disease.

Abstract: e19610 Background: Although there is a defined need for out-patient psychosocial care for cancer patients, data about out-patient psycho-oncological health care services and patients’ usage of ambulatory infrastructure outside certified cancer centres are scarce. Methods: We retrospectively analyzed charts and treatment protocols from 1,369 patients treated between 1998 and 2009 in a psycho-oncology (PO) practice retrieving socio-demographic and cancer-specific data plus data regarding PO intervention. Results: Of 1,180 patients analysed so far, 808 were documented cancer patients and 372 were relatives or friends of cancer patients. Median age of cancer patients was 50 (range 21-81) years, the majority being female (91%). Although PO interventions are not generally covered by most health care insurances in Germany, 87.7% of patients had public health insurance and only 12.7% had private insurance. 62,5% of patients (n=505) were diagnosed with breast cancer, followed by colorectal cancer (n=46), ovarian cancer (n=42), leukemia/lymphoma (n=38) and lung cancer (n=34), although all types of malignancies were represented. 60.1% received curative and 20.3% palliative treatment, while 19.6% could not specify their treatment intention. 503/663 (n=186 not specified) patients had at least one child with 39.5% being less than 18 years of age. 75.9% (176/232) had received high school education, and 37.1% (151/407) were actively working, while 40.3% (164/407) were incapable of work or on retirement pay (22.6%, 92/407). Half of the patients (50.2%) were Aachen residents, while the other half resided within a 50 km radius. Median number of therapy sessions was 12 (range 1-97). Other treatment specific aspects are still being analysed and will be presented at the meeting. Conclusions: Despite the clear demand for all cancer patients, the majority of cancer patients actively seeking out-patient psycho-oncological support are women with breast cancer, while men and other cancer subtypes are clearly underrepresented. Better information, optimized resources, allocation strategies and comprehensive coverage of PO services are needed in order to address more cancer patients with psycho-social distress.

Abstract: Ziel der Studie Familien mit einem onkologisch erkrankten Elternteil sind besonderen emotionalen und organisatorischen Belastungen ausgesetzt, unter denen v. a. minderjährige Kinder leiden. Um die Belastung der Familienmitglieder zu reduzieren und einen koordinierten Zugang zu sozialen und logistischen Unterstützungsmöglichkeiten zu schaffen, wurde das Modellprojekt Brückenschlag initiiert. Ziel des vorliegenden Beitrags ist, die Einführung dieses Projektes in Anlehnung an das Inanspruchnahme-Modell von Andersen bezüglich Akzeptanz und Inanspruchnahme zu evaluieren. Methodik In einer querschnittlich angelegten Beobachtungsstudie im Mixed-Methods-Ansatz wurden semi-strukturierte schriftliche Expertenbefragungen (n=10) und die Sekundäranalyse von Routinedaten des Versorgungsmodells (n=171 Familien) kombiniert. Ergebnisse Quantitative Sekundäranalyse: Die teilnehmenden Familien haben 1–7 Kinder (Median (M) 2, Spannweite (S) 6). In 66% der Fälle ist die Mutter erkrankt, in 20% ist das erkrankte Elternteil alleinerziehend. Die familiären Kommunikationsstrukturen werden als „mittelmäßig“ bis „ziemlich offen“ eingeschätzt. Von den insgesamt 171 Kontaktaufnahmen (Studienzeitraum 9/14 bis 11/17), wurde Brückenschlag von 133 Familien in Anspruch genommen. 59,2% der Kontakte entstanden über die Psychoonkologie und den Sozialdienst. Kam der Kontakt auf Initiative des Patienten selbst oder durch die Psychoonkologie zustande, so wird signifikant häufiger (p=0,047) eine Begleitung etabliert als bei anderen Kontaktpersonen. Qualitative Analyse: Es zeigt sich ein Mangel in der Bekanntschaft und Koordination vorhandener Unterstützungsangebote und an familiären Ressourcen, vorhandene Unterstützungsangebote in Anspruch zu nehmen. Sowohl von den Familien gewünschte als auch im Verlauf etablierte Unterstützung fallen vor allem in den Bereich organisatorischer Unterstützung. Brückenschlag erleichtert dabei die Netzwerkarbeit und übernimmt eine Lotsenfunktion für die Familien. Schlussfolgerung Die gesammelten Daten deuten darauf hin, dass Familien, die in ihren soziodemographischen Merkmalen dem deutschen Durchschnitt entsprechen, tatsächlich einen großen Bedarf an organisatorischer Unterstützung entwickeln, sobald ein Elternteil an Krebs erkrankt. Das Modellprojekt Brückenschlag schafft einen Zugang zu Unterstützungsleistungen für Familien mit einem krebserkrankten Elternteil.

Abstract: Introduction Recent studies indicate that particularly in a subgroup of younger patients, acute myeloid leukemia (AML) develops due to an inherited genetic predisposition linked to mutations in genes such as ANKRD26, SAMD9, SAMD9-L, GATA-2, genes causing telomere biology disorders or Shwachman-Diamond syndrome. However, the prevalence of so-called "AML predisposition syndromes" (APS) underlying newly diagnosed cases with AML is unknown. Actual screening strategies for APS are based on the family history and clinical/genetic features. There is growing evidence that APS frequently manifest themselves with an oligosymptomatic phenotype or are lacking specific symptoms altogether. Furthermore, molecular analysis of the clonal population without additional analysis of non-clonal cells do not allow the discrimination between inherited and acquired changes. Thus, new approaches to identify the subset of patients with underlying APS in adult newly diagnosed AML patients are needed. One frequent feature observed in APS is younger age at the time of diagnosis and the initial presence of an aberrant karyotype. Along this line, we retrospectively screened the German SAL-AML registry using age and the presence of an aberrant karyotype as pre-defining parameters to analyze the prevalence of APS in this selected cohort. Patients and methods The database of the German SAL-AML registry includes over 5207 patients with AML. We screened for patients below 35 years of age and with any type of numerical or structural chromosomal aberration at first diagnosis. DNA samples of patients achieving cytological remission (CR) and available samples of peripheral blood or bone marrow were selected. CR samples were chosen to reduce potential contamination by malignant AML blasts. Patients were screened for pathogenic variants using a self-designed NGS panel containing the entire coding sequences of ACD, ANKRD26, CTC1, DDX41, DKC1, ERCC6, ETV6, GATA1, GATA2, LIG4, NHP2, NOP10, PARN, POT1, RPA1, RPL11, RPL15, RPL26, RPL35A, RPL5, RPS10, RPS17, RPS19, RPS24, RPS26, RPS7, RTEL1, SAMD9, SAMD9L, SBDS, SRP72, TERC, TERF1, TERF2, TERT, TINF2, TPP1 and WRAP53. An inherited variant was considered in all patients with a variant allele frequency between 40-60% for heterozygous variants and & gt;90% for homozygous ones. To analyze the functional consequence of SAMD9 variants, proliferation assays with HEK293 cells transfected with the respective identified variant was carried out. Results and discussion On the basis of the inclusion criteria mentioned above, we were able to identify 41 patients. All cases except one were considered de novo AML by the treating physicians and received an anthracycline/cytarabine based induction chemotherapy. Mean age of the 41 patients was 26 ± 5 years (mean ± S.D.). Predominant karyotypic aberration were abnormalities of chromosome 8 (18/41) as well as a complex aberrant karyotype (29/41). NGS analysis revealed five different heterozygous mutations in approx. 10% (4/41) of patients: GATA2 c.1009C & gt;T p.(Arg337Ter), SBDS c.183_184delInsCT and c.258+2T & gt;C (both mutations in the same patient), TINF2 c.848C & gt;A p.(Pro283His), SAMD9 c.2854G & gt;C p.(Gly952Arg). The variants in GATA2, SBDS and TINF2 are known to be pathogenic. For SAMD9, in vitro experiments showed increased inhibition of cell growth compared to wild-type supporting the pathogenicity of the mutation. Focusing on the clinical outcome, 50% (2/4) of the identified APS patients received allogeneic transplantation during follow-up compared to 65% (24/37) in the group without detectable mutations. Median survival in the APS group was significantly shorter with 3.2 months compared to 105.3 months in the remaining 37 AML patients (p & lt;0.001). Conclusions Using age and karyotype as selection criteria, we were able to identify an inherited APS in 10% of newly diagnosed AML patients below 35 years with chromosomal aberrations reaching CR. Obviously, our study is limited by rather stringent inclusion criteria not allowing overall conclusions on the incidence of APS in newly diagnosed AML. However, age and karyotype might provide simple clinical parameters to trigger genetic screening for inherited APS in addition to the actual recommendations. Given the significant difference in survival in patients with and without underlying APS, our study clearly supports inclusion of screening for APS in this cohort pending prospective validation. Figure Disclosures Röllig: Amgen, Astellas, BMS, Daiichi Sankyo, Janssen, Roche: Consultancy; Abbvie, Novartis, Pfizer: Consultancy, Research Funding. Müller-Tidow:Daiichi Sankyo: Research Funding; Pfizer: Research Funding, Speakers Bureau; Janssen-Cilag GmbH: Speakers Bureau; BiolineRx: Research Funding. Panse:Blueprint Medicines: Consultancy, Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Chugai: Speakers Bureau; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Consultancy, Membership on an entity's Board of Directors or advisory committees; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees; Grunenthal: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Apellis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Brümmendorf:Pfizer: Consultancy, Honoraria, Other: Travel, Accommodation, Expenses, Research Funding; Novartis: Consultancy, Other: travel, accommodation, expenses, Research Funding; Janssen: Consultancy; Merck: Consultancy; Takeda: Consultancy. Jost:Roche: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Celgene: Other: travel support; JAZZ: Other: travel support.